Nitroaryldisulfide pesticide



United States Patent F NITROARYLDISULFIDE PESTICIDE John F. Harris, Jr.,Wilmington, Del., assignor to E. I. du Pont de Nemours and Company,Wilmington, Del., a corporation of Delaware No Drawing. Filed Aug. .27,1956, Ser. -No.%606,11s4

3 Claims. ((1167-30) This invention relates to biological toxicantcompositions, more particularly anti-bacterial,fungicidaL-and herbicidalcompositions, andmethodsiemploying as an essential active ingredient 2a'nitroaryl disulfideof the kind more particularly described below.

This application is a continuation-in-part of -my-coipending UnitedStates patent application .SerialNo. 447,- v653, filed August 3,l954,now abandoned. I

Despite the large number of biological toxicantcompositions which havebeen introduced in recent years, particularly for use ininhibitingbacterialffungal and higher forms of plantgrowth, it isnot-possible to readily deduce from the structure of a compoundwhethenornot it has biological toxicant activity. A further complexingfactor is the variation in biological activity of a compound. Activityoften varies with the specific variety of pest to be controlled :andwith the conditions of application.

To have a maximum effect, the biological'toxicant composition should beselective in its action. In other words, it should destroy or inhibitthe growth-of'the pest'orweed but should not interfere with the normalfunctioningof the host, or with the surrounding environment, =whetheranimal or plant crop. The composition should also be soluble, or atleast dispersible, in aqueous media 'because water is much preferred toorganic solvents in biological toxicant uses.

I have now found that these requirements are'm'et by biological toxicantcompositions containing as en essential active ingredient an aromaticdisulfide 'of "the formula where Ar is a'nitroaryl group, i.e., anaromatic hydrocarbon radical containingfrom l'to 2 "nitro'"groups,:and Yis a hydrocarbon group of l to carbons or'a'monofunctionally substitutedhydrocarbon. group containing up to 10 carbons including a salt'orsalt-forming group 'as a 'substituent. By the term salt and saltforminggr'oup I mean to include carboxyl radical, 'sulfonyl radical, andaryl radical of from 6 to 10 carbon atoms containing a nuclear hydroxylradical. Other monofunctionaljgroups which fall Within the scope of Y ofFormula 1 are carbonyl, alkoxycarbonyl and alkoxythiocarbonyl.

A typical example of a disulfide of the abovetype is dinitrophenyl ethyldisulfide,

omQs-s-mm which is effective against Escherichia coli, 6A, Micro--coccus pyogenes var. aureus, H Strain, and Streptococcus faecalis, 10Cl.If the ethyl group in this compound --is replaced by C H the resultantcompound is ineffective as an antibacterial agent. This markeddifference inactivity is attributed to the greater water solubilityo'f'the ethyl compound.

2,962,411 Patented Nov. 29,1960

Tobe sufliciently efiective forpractical use, the substituent on thesulfur to the right in Formula '1 should be either a hydrocarbon groupof not more than ten car bons or a hydrocarbon group containing asubstituent that enhances its water solubility, such as a salt orsaltforminggroup, e.g., carboxyl, sulfonic, or, phenolic hy droxyl.Particularly efiective compounds of this class are represented by theformula where Ar is an aromatic hydrocarbon, preferably phenyl,containing from 1 to 2 nitro groups and R is a hydrocarbon groupcontaining up to 9 carbon atoms.

Compounds represented by Formula 3 wherein Ar is a 'phenyl groupcontainingfrom 1 to'2 nitro-groups are fully described and claimed in mycopending-.joint-ap plication with Marvin 'Carmack, U.S. Serial No.408,020, filed February 3,, 1954, now abandoned. In 'brief, theunsymmetrical .nitrophenyl disulfides claimed in this co pending caseare prepared by reacting substantially equimolecular portions of asulfenyl halide of the formula ArSX where X is halogen, preferablychlorine or bromine, with -a mercaptoacid represented'by theIformulaH"S-R COOH where R is-an' open-chain hydrocarbon or an acyl substitutedopen-chain hydrocarbonradi- ;c'al. Alternatively, some of the disulfidescan .be pre- ;.pared bya dithiohalide (Ar'S hal) with aketenejfollowedby hydrolysis; or by reacting a dithiohalide with ethyl acetoacetate.

The disulfides used in this invention are conveniently prepared byreacting a nitroarylsulfenyl chloride with a mercaptan of'formula 'YASH,where 'Y hasthe meaning indicated in Formula 1. Thus, 2-nitrophenyl.carboxymethyl disulfide (4.),

can .be prepared by adding .ljpart of thioglycolic acid dissolved in 10parts of anhydrous ether to '2.6 parts of o-nitrobenz enesulfenylchloride dissolved in about 60 parts of anhydrous'ether; allowing themixture to 'standfor an hour; evaporating the mixture to dryness; andrecrystallizing the residue from benzene. 'The product"(4') thusobtained (approximately 3 parts) is a yellow sclid melting at 119-120"C.

The nitroaryl disulfides'use'd in the biological toxicant compositionsof the invention are in general characterized by bacterial andfungicidal activity at relatively low levels and herbicidal at higherconcentrations. For example, 2-nitrophenyl ethoxythiocarbonyl disulfideat levels of about 31 and p.p.m. is inhibitory to the growth of the'bacteria-Micrococcus pyogenes and Streptococcus faecalisrespectivelyyat 400 p.p.m., the compound controlled the fungus disease,bean rust (Uromyces appendiculatus) on :bean withoutjplant injury;whileat 10,000 p.p.m. the compound has pronounced herbicidal qualities asmeasured in ;foliar-sprays on tomato.

The biological toxicant compositions of theinventi'on :are prepared byadmixing one or more of the nitroaryl disulfides defined heretofore, inpesticidal or herbicidal effective amounts, with a conditioning agent orcarrier of the kind used and referred to in the art as a biologicaltoxicant adjuvant or modifier in order to provide formulations adaptedfor ready and efficient application using conventional equipment toareas in which it is desired to destroy or control the growth of weeds,unwanted "plants, bacteria, fungi, insects and other animal andplantpests In the application of nitroaryl disulfides of Formula 1 asbiological toxicants, particularly as anti-bacterial agents, thetoxicants are normally diluted to a desired concentration, say, 0.001 to1% or more by admixture with a suitable liquid or solid carrier. Thus,they can be dissolved or dispersed in water or organic solvents andapplied as liquids, or they may be admixed with solid carriers andapplied as dusts. Particularly eifective liquid compositions are thosebased on water containing a surface activeagent. Nitroaryl disulfidescontaining acid groups are conveniently used in the form of their sodiumor ammonium salts in water. Suitable solid carriers include finelydivided talc, sulfur, calcium carbonate and bentonite.

As already indicated, the pesticidal compositions may be made from amixture of nitroaryl disulfides since some of the disulfides are moreefiective towards certain pests than others, and the mixture produces agreater Todd, US. Patent Nos. 2,65 5,444-447.

The herbicidal method of the present invention comprises applying anaryl carboxyalkyl disulfide of Formula 1, ordinarily in a herbicidalcomposition of the aforementioned type, to the locus or area to beprotected from undesirable plant growth. The active compound is, of

course, applied in sufiicient amount to exert the desired herbicidalaction. The application can be made directly upon the locus or area andthe vegetation thereon during the period of infestation. Alternatively,the application can be made in advance of an anticipated weedinfestation.

The dosage employed can be determined readily by those skilled in theart by conventional techniques. It is, of course, dependent upon theparticular active ingredient employed, the nature of the formulationused, the type of treatment, the type of vegetation to be controlled,climatic conditions and the like. when applied as a foliar spray, adosage of about 20 to 60 pounds per acre is used.

This method is applicable to the control of both broad leaf and grassyannual and perennial weeds, such as yellow foxtail, Johnson grass, wildmustard, dandelion and Lambs-quarters. It has particular utility as acontact agent for the control of annual broad leaves, such asLambs-quarters, ragweed, pigweed and annual grassy weeds, such as yellowfoxtail and crabgrass.

In order that the invention can be better understood, the-followingexamples are given in addition to those set forth above:

EXAMPLE I Agar plate-paper disc method This method for testingantibacterial compositions was carried out as follows: Selected testbacteria were grown in 2% tryptose broth for 18-24 hours at 37 C. Thetest organism was then inoculated into melted 2% tryptose agar and thispoured into sterile petri plates and allowed to harden. Paper discsimpregnated withthe disulfides to be tested were then placed on thesurface of the inoculated agar plates and the plates incubated at 37 C.for 18-24 hours. The paper discs were of sterile /2" diameter filterpaper. They were impregnated with a solution obtained as follows. Atotal of 50 mg. of the disulfide was dissolved in 5 ml. of acetone. Ofthis acetone solution, 0.1 ml. was used to treat the disc after whichthe acetone was evaporated. The final concentration of compound per discwas 1000 micrograms (1000ug). I

In general, h

The width of the zone of inhibition of bacterial growth surrounding thepaper disc was measured. This zone corresponds to the absence of allgrowth of the test organism and is indicative of the potency of thecompound tested. In Table I, the zones of inhibition (in mm.) are shownfor the following compounds:

A:2-nitrophenylcarboxymethyl disulfide (M.P. 1l9-120 TABLE I [Zones ofinhibition (in mm.)]

Micrococcua Pseudomonaa Compound pyogenea var. Streptococcusaerugz'nosa,

aureus, E faecalis, 1001 Temple Strain Strain The two numbers in theabove table represent results of duplicate assays.

EXAMPLE II T ube dilution assay In this test tube dilution assay, eachof the above compounds (A, B, C, D and E of Example I) was tested todetermine the minimum concentration at which it would prevent bacterialgrowth. Ten milligrams of each compound was dissolved in a small amountof acetone containing sodium bicarbonate and the mixture was diluted to10 ml. with sterile 2% tryptose broth. A series of six test tubes (1, 2,3, etc.) each containing 2 ml; of sterile 2% tryptose broth wasprepared. A total of 2 ml. of the solution containing the test compoundwas added to tube 1, the solutions thoroughly mixed, and 2 ml. from thelatter tube transferred to tube 2. After mixing, this procedure Wasrepeated for the other tubes with 2 ml. from the final tube beingdiscarded; The tubes contained the following concentrations of compound:Tube 1:500 ,og/mL; Tube 2:250 ,ug./Inl.; Tube 3:125 g/mL; Tube 4=62.5,ug./ml.; Tube 5:

31.25 ng/mL; and Tube 6=15.6 ,og./m1.

Cultures of the test organisms were grown in 2% tryptose broth for 18-24hours at 37 C. and diluted 1:10 in sterile tryptose broth. Tubes 1-6along witha control were inoculated with 0.1 ml. of the 1:10 culturedilutions and the tubes incubated at 37 C. for 18-24 hours and examinedfor presence or absence of growth. In Table II are recorded the resultsof duplicate assays for each of the compounds expressed in terms of aconcentration (in micrograms per ml.) at and above which no bacterialgrowth occurred.

Test Organisms Compound .Micmcoccus pz ogenes var.

ELLTB'ILS Streptococcus faecalz's momenta EXAMPLE III 'IUBE-DI LU P IONASSAY Following the procedure used in Examples I and II, Mimmcusplate-disc and tube-dilution assays were made of 2,4- l ggggii gg gdinitrophenyl ethyl disulfide with the following results: 5 H snafuPLATE-DISC ASSAY 31-25 [Zone of inhibition in mm.] EXAMPLE IV I I 110The general method of Example H 'was used to detergglggifi mine theminimum concentration to prevent hate'fial au1'eus,HStrain growth of asenes of compounds contalnlng amtroaryl SS-group. The following tablelists the structuralfo-rmu- 20,20 17,17 15 la of the coinpound, itsmelting point and 'the'inhibitory concentration in micrograms per ml.

TABLE Compound Inhibitory Concentration Micrococcus Strefifdcbc'cu-sStructural Formula M.P., O. pyogenes .faecalis var. aureus N02 Ossomc00H, 111-112 31. 25 15. s

j Ores-S0100 H3 7 141. 5-142. 5 s2. 5 500 OSSOOH 151-151. 5 i 15. 6 15.s

- ssogm 30.5-31. 5 15. s 62.5

TABLE-Continued Compound Inhibitory Concentration MicrococcusStreptococcus Structural Formula M.P., C. puogenes ecalz's V211. aureusN 02 Gsswmno OH 125-127 15.6 31. 25

i ss-o 0 01m 64-64. a1. 125

N02 omGss-(cmnooon mas-130.5 15.5 31.25

NO2- coon v 1 OSSO V 4 223-224 15.6 125 I O-SS-CH 53-54 15.6 15.6

II C -ssc-0H4 71. 5-78. 5 15.6 15.6

swine-O as. 5-84. 5 s1. 25 500 N02 omOss-mmon 46-47 31. 25 52.5

omQ-ssornc 0 011 96-97 15.6 15.6

oiN SSCaH1i(D) 44-44. 5 125 125 0m SS-C9H1D as. 5-41 15. a 125 OZNssonicmo o 0 CH: 65. 5-66 62.5 125 Additional examples of nitroaryldisulfides employed in the pest control compositions and methods of theinvention are: Z-nitrophenyl-2-carboxyethyl disulfide, 2,4-dinitrophenyl-3-carboxypropyl disulfide, dinitronaphthyl carboxymethyldisulfide, and the following 2,4-dinitr0- phenyl disulfides of formula(NO C H SS'-Y, where Y is: CH C3H7, CH CH=CH /GHz-CH: Osona and onpesticidal compositions of the invention. The numbers following thetabulated ingredients represent parts by weight of the ingredients inthe respective compositions.

EXAMPLE V Dust formulation 7 The dust was made by blending or mixing theingredients and grinding the mix to give compositions having an averageparticle size less than about 50 microns.

2,4-dinitrophenyl ethyl disulfide 20 Talc EXAMPLE VI Granularcomposition The composition was readily prepared by mixing theingredients with water to form a paste. The paste was then dried undervacuum at 60 C. and ground to give .the desired granular size.Preferably the granules will be in the order ofone-thirty' second toone-quarter inch diameter.

2,4-dinitrophenyl carboxyme'thyl disulfide Goulac 1 3 Hydrocarbon oil s:1

Dextrin Hydrated silica (Celite) 66 EXAMPLE VII Liquid dispersioncomposition The composition was prepared by dispersing the biologicallyactiveingredient in water by means of a surface active agent.

'o-Nitrophenyl=5=carboxypentyl disulfide 1 Sodium laur'yl sulfate 1'Water 98 MPLE VIII Water-dispersible powder The powdered compositionwas made by intimately mixing the listed ingredients using conventionalmixing or blending equipment and then grinding the mixture to give apowder.

o-Nitrophenyl-Z-carboxyethyl disulfide 87.8

Hydrated silica (Celite) 10.9

Sodium lauryl sulfate, 50% 1.3

EXAMPLE IX Antibacterial soap The following composition was made bymixing the finely ground disulfide with a soap:

2,4-dinitrophenyl-2-carboxyethyl disulfide 1 Liquid soap 99 EXAMPLE XThis example demonstrates the practice of the present method employingwettable powder herbicidal compositions containing as an activeingredient a compound of Formula 1. The wettable powder compositions areprepared by combining the dry ingredients, blending in a ribbon blender,micropnlverizing in a hammer mill until substantially all of the productis below 50 microns in particle size, and reblending the product in aribbon blender to give a free flowing powder that is readily dispersiblein water to form dilute sprayable formulations.

Percent 2,4-dinitrophenyl ethyl disulfide 80 Calcium silicate 18.75Alkyl aryl sulfonate 1.0 Methyl cellulose 0.25

2-nitrophenyl carboxymethyl disulfide 50 Bentonite 20 Diatomaceous earth30 These compositions are extended with water to form sprayableformulations containing 1% by weight of the active ingredient. They arethen applied using a compression type hand sprayer rig as directedpost-emergence treatments in agricultural plots planted to corn andinfested with broad leaf weeds. These treatments give excellentpost-emergence weed control with no substantial damage to the corn crop.

10 EXAMPLE XI This example demonstrates the present herbicidal methodsusing aqueous solutions containing as active ingredients compounds ofFormula 1. These solutions are prepared by slowly adding thewater-soluble nitroaryl disulfide derivatives to water under agitation,heating to hasten solution when necessary. .A wetting agent is includedin some of the formulations to reduce the surface tension and aid incoverage of the foliage to which the solution is to be applied.

Percent Z-nitrophenyl Z-carboxyethyl disulfide 30 Sodium lauryl sulfates I 2 Water- 68 2 nitrophenyl S-carboxypentyl disulfide 25 SodiumNmethyl-N-oleoyl laurate '5 Water a 70 These aqueous solutions arediluted with water to an active ingredient content of 2% by weight.'They are then applied with a sprayer mounted on a railroad car to wetthe foliage thoroughly. Excellent control of sprayed weeds is obtainedby this treatment.

EXAMPLE XII This example demonstrates the practice of the present methodusing dust herbicidal compositions. These dusts are made by firstblending and grinding the active aryl carboxyalkyl disulfides with theminor absorptive diluent until the particle size of the activeingredient is substantially less than 50 microns, and then blending themixture with the major, free flowing, dense diluent in a Thesecompositions when applied by hand around the base of telephone poles atthe rate of pound/sq. rod effectively control the weeds growing in thetreated area.

EXAMPLE XIII This example illustrates the preventive fungicidal actionof the nitroaryl disulfides of Formula 1. The disulfides were sprayedfrom an aqueous solution onto bean plants which were infected with beanrust (Uromyces appendiculatus). One week later, the plants thus treatedwere compared with untreated plants. The following data were obtained:

Active Ingredient Dosage, Percent Percent Disease 2,4dlnitrophenyl ethyldisulfide 0. 2 19 21 -Initrophenyl ethoxythiocarbonyl disulfide 0. 04 1.5 on a Percent disease as used above is calculated with relation to theuntreated or control plants which are taken for comparative purposes asbeing 100% diseased.

Those skilled in the art will appreciate that other pesticidalcompositions of the invention, including tooth paste, creams, oils,alcoholic solutions and concentrates,

standing only and no unnecessary limitations are to be understoodtherefrom.

I claim:

1. A method for controlling bacterial and fungal pests which comprisesapplying to areas to be protected, in amount sufiicient to exert abiological toxicant action, a nitroaryl disulfide of the formula Ar-S-SYwhere Ar is an aromatic hydrocarbon having from 6 to 10 carbon atoms andcontaining from 1 to 2 nitro groups, and Y is a hydrocarbon group havingfrom 1 to 10 carbon atoms, said group being selected from the classconsisting of unsubstituted hydrocarbyl radicals and monosubstitutedhydrocarbyl radicals in which the substituents are selected from theclass consisting of carboxyl, carbonyl, alkoxycarbonyl,alkoxythiocarbony], sulfonic, and hydroxyaryl radicals.

I 2, A method of combatting bacterial and fungal pests which comprisessubjecting the pest to the action of a composition comprising a compoundof the formula ;Ar-S--S-RCOOH where Ar is a nitroaryl group and R is ahydrocarbon group containing up to 9 carbon atoms, said group beingselected from the class consisting of alkylene, aryleue, andcycloalkylene radicals.

3. A fungicidal composition comprising an inert fungicidal adjuvant as acarrier therefor, and, as an essential active ingredient in admixturetherewith, o-nitrophenyl ethoxythiocarbonyl disulfide.

References Cited in the file of this patent UNITED STATES PATENTS OTHERREFER]:Nexis Talen: Chem. Abst., vo1. 22 (1928), page 3652.

UNITED STATES PATENT OFFICE CERTIFICATION OF CORRECTION Patent No.2,962,417 November 29 1960 John F, Harris, Jr.

It is hereby certified that error appears in the above numbered patentrequiring correction and that the said Letters Patent should read ascorrected below.

Column 7, lines 64 to 68, in the formula, the ring carbon to which theCl is attached should have only one H; column 10, line 35, after"diluent in a" insert ribbon blender. column 12, line I after "group".insert having from 6 to 10 carbon atoms Signed and sealed this 16th dayof May 1961.

(SEAL) fittest:

ERNEST W. SWIDER DAVID L. LADD Attesting Officer Commissioner of Patents

1. A METHOD FOR CONTROLLING BACTERIAL AND FUNGAL PESTS WHICH COMPRISESAPPLYING TO AREAS TO BE PROTECTED, IN AMOUNT SUFFICIENT TO EXERT ABIOLOGICAL TOXICANT ACTION, A NITROARYL DISULFIDE OF THE FORMULAAR-S-S-Y WHERE AR IS AN AROMATIC HYDROCARBON HAVING FROM 6 TO 10 CARBONATOMS AND CONTAINING FROM 1 TO 2 NITRO GROUPS, AND Y IS A HYDROCARBONGROUP HAVING FROM 1 TO 10 CARBON ATOMS, SAID GROUP BEING SELECTED FROMTHE CLASS CONSISTING OF UNSUBSTITUTED HYDROCARBYL RADICALS ANDMONOSUBSTITUTED HYDROCARBYL RADICALS IN WHICH THE SUBSTITUENTS ARESELECTED FROM THE CLASS CONSISTING OF CARBOXYL, CARBONYL,ALKOXYCARBONYL, ALKOXYTHIOCARBONYL, SULFONIC, AND HYDROXYARYL RADICALS.